A Study to Evaluate Isavuconazonium Sulfate for the Treatment of Invasive Aspergillosis (IA) or Invasive Mucormycosis (IM) in Pediatric Participants

NCT03816176 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 9766-CL-01072018-003975-36
• Study Type: interventional
• Target: 31
• Locations: 3 countries
• Sites: 10

Brief Summary

The purpose of this study was to evaluate the safety, tolerability, and efficacy of isavuconazonium sulfate in pediatric participants.

Conditions

Invasive Mucormycosis; Invasive Aspergillosis

Keywords

ASP9766; Cresemba; BAL8557; isavuconazonium sulfate

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  An AE is any untoward medical occurrence in a participant administered a study drug, which does not have to have a causal relationship with this treatment. It can be any unfavorable sign, symptom, or disease temporally associated with the use of a medicinal product. TEAE is defined as an AE observed after starting administration of the study drug through 30 days after the last dose.

  From first dose to 30 days after the last dose (maximum 210 Days)

• Percentage of Participants With All - Cause Mortality Through Day 42

  All - Cause Mortality Through Day 42

  Baseline up to 42 days

Secondary Outcomes (9)

• Percentage of Participants With All - Cause Mortality

  Baseline up to day 84 and end of treatment (EOT) (up to a maximum of 180 days) (Average duration of treatment: 57.7 days)

• Percentage of Participants With Overall Response: Adjudication Committee (AC) Assessment

  Baseline up to days 42, 84 and EOT (180 days)

• Percentage of Participants With Clinical Response: AC Assessment

  Baseline up to days 42, 84 and EOT (180 days)

• Percentage of Participants With Clinical Response: Investigator Assessment

  Baseline up to days 42, 84 and EOT (180 days)

• Percentage of Participants With Radiological Response: AC Assessment

  Baseline up to days 42, 84 and EOT (180 days)

Study Arms (1)

Isavuconazonium sulfate

EXPERIMENTAL

Participants received 10 milligrams/killograms (mg/kg) dose of isavuconazonium sulfate every 8 hours (± 2 hours) on days 1 and 2 for a total of 6 doses (via intravenous or oral administration at the investigator's discretion) followed by once-daily maintenance dose of 10 mg/kg for up to 84 days IA or 180 days IM or until the participant had a successful outcome as judged by the investigator, whichever occured first. The route of administration could have been changed per the investigator's discretion.

Drug: Isavuconazonium sulfate

Interventions

Isavuconazonium sulfate DRUG

Intravenous (IV) infusion

Also known as: Cresemba

Isavuconazonium sulfate

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject diagnosed with IA or IM. A positive diagnosis is defined as follows:
• Proven, probable or possible IFI per the European Organisation for Research and Treatment of Cancer/Mycoses Study Group \[EORTC/MSG\], 2008 criteria Note: Subjects with "possible" IFI will be eligible for enrollment; however, diagnostic tests to confirm the invasive fungal disease as "probable" or "proven" according to the EORTC/MSG criteria should be completed within 10 calendar days after the first dose of study drug
• Note: In addition to the criteria set for mycological criteria by the EORTC/MSG in 2008, and only for subjects with an underlying hematologic malignancy or recipients of hematopoietic stem cell transplant (HSCT) who also have clinical and radiologic features consistent with invasive fungal infection, the following are acceptable:
• Galactomannan (GM) levels (optical density index) meeting the below criteria are acceptable mycological evidence for enrollment or upgrading the diagnosis to probable IA:
• \. A single value for serum or bronchoalveolar lavage (BAL) fluid of ≥ 1.0 or
• \. Two serum GM values of ≥ 0.5 from two separate samples
• Subject has sufficient venous access to permit intravenous administration of study drug or the ability to swallow oral capsules
• A female subject is eligible to participate if not pregnant and at least one of the following conditions applies:
• Not a subject who is of childbearing potential, OR
• Subject who is of childbearing potential who agrees to follow a contraceptive guidance throughout the treatment period and for at least 30 days after the final study drug administration
• Subject and subject's parent(s) or legal guardian agree that the subject will not participate in another interventional study while on treatment with the exception of oncology trials

You may not qualify if:

• Subject has familial short QT syndrome, is receiving medications that are known to shorten the QT interval, or has a clinically significant abnormal ECG
• Subject has evidence of hepatic dysfunction defined as any of the following:
• Total bilirubin (TBL) ≥ 3 times the upper limit of normal (ULN)
• Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 5 times the ULN
• Known cirrhosis or chronic hepatic failure
• Subject has used strong cytochrome P450 (CYP3A4) inhibitors or inducers such as ketoconazole, high dose ritonavir, rifampin/rifampicin, long acting barbiturates (e.g., phenytoin), carbamazepine and St. John's Wort in the 5 days prior to the first dose of study drug
• Subject has another IFI other than possible, probably or proven IA or IM
• Subject has chronic aspergillosis, aspergilloma or allergic bronchopulmonary aspergillosis
• Subject has received mould active systemic antifungal therapy, effective against the primary IMI, for more than four days during the seven days preceding the first dose
• Note: Prior use of prophylactic antifungal therapy is acceptable. In case of breakthrough IA while on prophylactic mould-active azole class drugs, additional documentation will be required to be submitted to the sponsor medical monitor or designee to approve subject enrollment
• Subject has known history of allergy, hypersensitivity or any serious reaction to any of the azole class antifungals, or any components of the study drug formulation
• Subject has any condition which makes the subject unsuitable for study participation
• Subject is unlikely to survive 30 days
• Subject has received investigational drug, with the exception of oncology drug trials, or trials with investigational drugs treating graft versus host disease, within 28 days or five half-lives, whichever is longer, prior to screening

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (10)

Children's Hospital, Los Angeles

Los Angeles, California, 90027, United States

Location

University of California - Los Angeles

Los Angeles, California, 90095, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Site BE32001

Ghent, 9000, Belgium

Location

Site BE32002

Leuven, 3000, Belgium

Location

Site ES34002

Barcelona, 8035, Spain

Location

Site ES34003

Madrid, 28009, Spain

Location

Site ES34001

Madrid, 28041, Spain

Location

Related Publications (1)

• Segers H, Deville JG, Muller WJ, Manzanares A, Desai A, Neely M, Bordon V, Hanisch B, Lassaletta A, Fisher BT, Autmizguine J, Groll AH, Sinnar S, Croos-Dabrera R, Engelhardt M, Jones M, Kovanda LL, Arrieta AC. Safety, outcomes, and pharmacokinetics of isavuconazole as a treatment for invasive fungal diseases in pediatric patients: a non-comparative phase 2 trial. Antimicrob Agents Chemother. 2024 Dec 5;68(12):e0048424. doi: 10.1128/aac.00484-24. Epub 2024 Nov 14.

  PMID: 39540734 DERIVED

Related Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

MeSH Terms

Interventions

isavuconazole

Results Point of Contact

• Title: Clinical Transparency
• Organization: Astellas Pharma Global Development, Inc

astellas.resultsdisclosure@astellas.com

8008887704

Study Officials

• Executive Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2019
• First Posted: January 25, 2019
• Study Start: August 22, 2019
• Primary Completion: December 14, 2022
• Study Completion: December 14, 2022
• Last Updated: December 5, 2024
• Results First Posted: September 21, 2023

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); BE (2); US (5)